Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention in South Africa: Is There a Will and a Way?

Abstract

Human immunodeficiency virus (HIV) antiretroviral therapy (ART) use results in substantial improvements in HIVrelated morbidity and mortality [1, 2] and leads to dramatic reductions in sexual transmission of HIV among heterosexual serodiscordant couples when ART suppresses HIV viremia in the infected partner [3]. Yet 6000 new HIV infections continue to occur daily across the globe. Use of oral antiretrovirals as chemoprophylaxis has substantial potency for HIV prevention among diverse populations [4–8]. However, effectiveness is highly dependent on consistent daily or neardaily product use. For women, even morerigorous adherence may be necessary to realize optimal protection [9], a finding borne out by complete abrogation of effectiveness when either oral or topical vaginal preparations are used infrequently [10, 11]. Long-acting injectable antiretroviral (ARV) preparations, ideally administered bimonthly or quarterly, have the potential to obviate the need for daily dosing, thereby improving adherence during exposure events, and, in theory, maximizing reductions in HIV infection incidence. In this issue of The Journal of Infectious Diseases, Walensky et al provide important additional context for the advent of long-acting injectable preexposure prophylaxis (PrEP). Although the medication costs after approval of these agents are unknown, the authors present a well-considered modeling exercise of the type we have come to expect from the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) group, demonstrating potential advantages and costs, as well as cost-effectiveness thresholds for the use of long-acting injectable PrEP for young South African women. This work builds on previous studies by the same authors that evaluated daily oral PrEP in a similar theoretical cohort [12]. The authors propose a base case rooted in an almost unthinkably high-incidence population, in which the cumulative lifetime probability of HIV acquisition is >60%. Initially, looking at use during the 18–25 years of age timeframe, the CEPAC model predicts substantial improvements in cumulative lifetime risk of HIV acquisition and life expectancy, compared with no PrEP, and an incremental improvement over standard daily oral PrEP. Similarly, the incidence of HIV infections and HIV-related deaths during the 5-year period of treatment are reduced incrementally, compared with standard PrEP. Both standard PrEP and long-acting PrEP are cost saving in this scenario, with long-acting PrEP costing an incremental $150 per year of life saved, compared with standard PrEP. Fascinatingly, despite initial higher up-front financial investment costs for programmatic scale-up, in the long-run (after approximately 30 years), long-acting PrEP actually is the most cost-saving intervention, driven by overall reduced HIV infection incidence and HIV treatment and care costs. It would be interesting to re-model the cost-effectiveness of standard PrEP and long-acting PrEP after considering the lifetime postseroconversion costs of ART implied by the new World Health Organization guidelines that recommend ART for all who are HIV infected, although such guidelines will likely only increase the cost efficiency of any HIV prevention intervention, including all PrEP modalities. Importantly, extensive sensitivity analyses demonstrate the robustness of the findings against the obligate assumptions intrinsic to working with mathematical models. As the overall population-level HIV incidence declines, long-acting PrEP is no longer cost saving; however, it is still very cost-effective as compared to standard PrEP(incremental cost-effectiveness ratio, $680 per year of life saved as the incidence halves from the base case). Interestingly, even longer use of long-acting PrEP (ie, past the age of 25 years) only incrementally increases costs but has impressive impact on reductions in the lifetime HIV risk, whereas shorter durations of use (eg, only to 19 years of age), while requiring less investment of capital, do not avert enough HIV infections to make that smaller investment cost-effective. This finding highlights the importance of a nuanced and thorough understanding of the acceptability and predictors of persistence to injectable PrEP required to optimize prevention benefits. In a sobering analysis, the authors note that, to achieve 50% coverage of high-risk young women in South Africa, it would cost $1.6 billion over 5 years. This signals the massive investment that would be required to deploy and scale-up injectable PrEP use, assuming that its safety and efficacy are demonstrated. This dollar Received and accepted 29 October 2015. Correspondence: R. J. Landovitz, UCLA Center for Clinical AIDS Research and Education, 11075 Santa Monica Blvd, Ste 100, Los Angeles, CA 90025 (rlandovitz@mednet.ucla.edu). The Journal of Infectious Diseases © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. DOI: 10.1093/infdis/jiv524